ETFDH Gene: Electron Transfer Flavoprotein Dehydrogenase
Essential for mitochondrial fatty acid oxidation and amino acid metabolism
Gene Information Card
| Symbol | ETFDH |
|---|---|
| Full Name | Electron Transfer Flavoprotein Dehydrogenase |
| Gene Type | Protein coding |
| Chromosomal Location | 4q32.1 |
| NCBI Gene ID | 2110 ncbi.nlm.nih.gov/gene/2110 |
| Ensembl ID | ENSG00000171503 |
| UniProt ID | Q16134 |
| OMIM ID | 231675 |
| HGNC ID | 3483 |
| Aliases | ETF-QO, ETF-ubiquinone oxidoreductase, MADD |
Description
The ETFDH gene encodes electron transfer flavoprotein dehydrogenase (ETF-QO), a mitochondrial enzyme that transfers electrons from electron transfer flavoprotein (ETF) to the ubiquinone pool in the respiratory chain. This process is critical for the oxidation of fatty acids, amino acids, and choline. Mutations in ETFDH cause multiple acyl-CoA dehydrogenase deficiency (MADD), also known as glutaric aciduria type II, which can be riboflavin-responsive or non-responsive.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Multiple acyl-CoA dehydrogenase deficiency (MADD) | Loss-of-function mutations impair electron transfer, leading to accumulation of acyl-CoA intermediates and metabolic acidosis | ClinVar, OMIM |
| Glutaric aciduria type II | Same as MADD; caused by biallelic ETFDH mutations | OMIM |
| Riboflavin-responsive MADD | Certain ETFDH variants respond to high-dose riboflavin therapy, improving clinical outcome | ClinVar, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Skeletal muscle | 10.2 | High |
| Heart | 9.8 | High |
| Kidney | 7.3 | Medium |
| Brain | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 14.0 | Hepatocyte-derived |
| HeLa | 8.5 | Cervical cancer |
| K562 | 6.2 | Leukemia |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.250G>A (p.Ala84Thr) | Missense | Common in Asian populations | Reduced enzyme activity, riboflavin-responsive |
| c.770A>G (p.Tyr257Cys) | Missense | Rare | Loss of function, severe MADD |
| c.1285C>T (p.Arg429*) | Nonsense | Rare | Premature truncation, complete loss of function |
Mutation functional classification
Loss of Function (LOF)
Most ETFDH mutations cause loss of function, reducing or abolishing ETF-ubiquinone oxidoreductase activity, leading to MADD.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative effects described; MADD is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Fatty acid degradation (KEGG: hsa00071)
• Valine
• leucine and isoleucine degradation (KEGG: hsa00280)
• Metabolic pathways (KEGG: hsa01100)
• Electron transport chain (Reactome: R-HSA-611105)
Protein Summary
The ETFDH protein (ETF-ubiquinone oxidoreductase) is a 67 kDa mitochondrial flavoprotein that accepts electrons from reduced ETF and transfers them to ubiquinone (coenzyme Q). It contains a 4Fe-4S cluster and FAD cofactor. The enzyme is anchored to the inner mitochondrial membrane and is essential for the electron transfer from multiple dehydrogenases involved in fatty acid and amino acid catabolism.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ETFDH Knockout HEK293 Cell Line | EDJ-KQ3814 | Human | 2110 | Details Get a Quote |
| ETFDH Knockout A-549 Cell Line | EDJ-KQ27202 | Human | 2110 | Details Get a Quote |
| ETFDH Knockout HCT 116 Cell Line | EDJ-KQ27204 | Human | 2110 | Details Get a Quote |
| ETFDH Knockout HeLa Cell Line | EDJ-KQ27205 | Human | 2110 | Details Get a Quote |
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